Cytomegalovirus (CMV) is the most common congenital viral infection in humans occurring in one percent of all live births. Although most infections are not associated with clinical symptoms, five to ten percent of infected infants will exhibit clinically apparent disease at birth. Furthermore, 80 percent of infants with symptomatic infections will suffer residual neurologic abnormalities. Acquisition of CMV after birth is also frequent and usually occurs as a result of delivery through an infected genital tract or ingestion of breast milk containing infectious virus. Perinatal acquisition of CMV is usually asymptomatic and not associated with documented neurologic abnormalities. The mechanism of resistance to infection and CMV-induced disease are poorly understood, but are thought to be primarily immunologic. Although cellular immunity has been shown to be important in controlling CMV infections, recent evidence has suggested that anti-CMV antibody may play an equally important role in the transmission and virulence of CMV infections in utero and during the perinatal period. Antibody responses to different CMV-encoded proteins may vary among individuals and, therefore, strongly influence the acquisition and virulence of CMV infection. Initially, we will characterize the translational products of CMV recognized by the human immune response using a variety of immunochemical methods and panels of CMV-specific monoclonal antibodies. Using recently developed methodology, we wil compare the antibody response to different CMV-encoded proteins in infants acquiring CMV in utero and during the perinatal period to the response of infants who remained uninfected. Similarly, we will compare the response in infants with virulent in utero infections and those with asymptomatic infections. These studies should provide a comprehensive understanding of the role of antibody in the pathogenesis of congenital and perinatal CMV infections as well providing a greater understanding of the human immune response to CMV.